Euphorbia clusiifolia is a shrub with scandent stems that can reach lengths of 1–3 meters. The flowering branches are slender, measuring 2–4 mm in diameter, and are entirely glabrous. The leaves are simple and arranged oppositely in a decussate or occasionally distichous pattern. Leaf blades range from oblanceolate to oblong or occasionally elliptic, measuring 35–140 mm long and 10–45 mm wide, with broadly acute to rounded apices and cuneate to rounded, often oblique bases. The entire leaf surface is glabrous, and margins are smooth. Petioles are short (2–3 mm) and may be glabrous or slightly pilose at the base. Stipules are acute-triangular, 1–2 mm long, with erose and ciliate margins. The flowers are arranged in cyathia, either solitary or in many-branched, open cymose inflorescences of 3–8(–12). Peduncles range from 6–23 mm long and are pilose. The involucre is broadly campanulate, 2–2.5 mm high and 3–4 mm wide, with noticeable pilosity beneath the purple glands, which are also pubescent. As with all Euphorbia, the flowers are highly reduced and unisexual. The pistillate flower sits on a gynophore, while staminate flowers are grouped in cymules of one or more. There are no petals or sepals. Slender bracteoles subtend the single stamen in each male flower. The ovary is superior, and the red styles are bifid about one-third of their length, with thickened stigmas. The fruits are glabrous green capsules, 6–9 mm long, with a single ruga per face separated by sutures. They are borne on recurved gynophores, exserted 3–9 mm from the involucre. Seeds are reddish brown, smooth, subglobose, and measure 2.5–3 mm in length. It is found in mesic to wet forests between 300-500 meters.